Menu

Filter articles published since 2015 by topic, disease, or article type.

Guidlines for filtering

Results are filtered to show all matching articles from a particular category, and to show only articles that match all selected categories.

For instance, if "Biomarkers" and "Genetics" are selected in the Topic category, and "Multiple sclerosis" is selected in the Disease category, all results that match EITHER the Biomarkers OR Genetics Topic category will be shown, but only if they also match the Multiple sclerosis Disease category; i.e. Boolean search of [("Biomarkers" OR "Genetics") AND "multiple sclerosis"]

Filter articles published since 2015 by topic, disease, or article type.

Guidlines for filtering

Results are filtered to show all matching articles from a particular category, and to show only articles that match all selected categories.

For instance, if "Biomarkers" and "Genetics" are selected in the Topic category, and "Multiple sclerosis" is selected in the Disease category, all results that match EITHER the Biomarkers OR Genetics Topic category will be shown, but only if they also match the Multiple sclerosis Disease category; i.e. Boolean search of [("Biomarkers" OR "Genetics") AND "multiple sclerosis"]

Do Membraneless Organelles Host Fibril Nucleation?

Two proteins involved in amyotrophic lateral sclerosis (ALS) precipitate formation of cellular granules by condensing into liquid droplets, according to recent studies. One, called hnRNPA1, forms transient stress granules by a process known as liquid-liquid demixing, report co-senior authors Paul Taylor and Tanja Mittag at St. Jude Children’s Research Hospital in Memphis, Tennessee, in the September 24 Cell. In other words, when a sufficient number of hnRNPA1 molecules condense together, they form a drop of liquid distinct from the surrounding cytosol. A better-known ALS protein, FUS, self-coalesces into liquid organelles that interact with RNA polymerase, report senior author Nicolas Fawzi and colleagues in the October 15 Molecular Cell. Fawzi and co-authors at Brown University in Providence, Rhode Island, also found that the structure of liquid FUS remains amorphous after condensation.

Both FUS and hnRNPA1 contain low-complexity domains, stretches of sticky amino acids that can mediate aggregation. Each research group was struck by the propensity of pure FUS or hnRNPA1 to condense into liquid droplets. In Cell, first author Amandine Molliex and colleagues report that hnRNPA1 also turns liquid inside cells. A disease-linked hnRNPA1 mutation also assembled into droplets.

From these droplets, both wild-type and mutant hnRNPA1 solidified into fibrils, though the mutant did so at a faster rate. The authors posit that a small amount of fibrils might have some beneficial function, such as stabilizing the granules while the cell needs them, but too many fibrils could become pathological.

Scientists earlier determined that FUS, too, promotes liquid formation (see Sep 2015 news), which is supported by the new findings reported in Molecular Cell. First author Kathleen Burke and colleagues used nuclear magnetic resonance spectroscopy to determine the three-dimensional position of individual residues in the FUS low-complexity domain. This region, which assumes no stable secondary structure, seems essential for FUS to condense into a liquid. When monomeric in solution, the region flapped loose, with little in the way of ordered conformation. Once FUS condensed in vitro, the low-complexity domain remained disordered, despite being more viscous. That implies the droplets were indeed liquid. They were not rigid structures such as aggregates or gels, which are solidified protein conglomerations long implicated in neurodegeneration.

FUS normally localizes to sites of transcription, so the authors examined the interaction between FUS liquid drops and RNA polymerase II. The carboxyl-terminal domain of that enzyme was able to nucleate FUS condensation and attached itself to the droplets, hinting that transcription occurs there.

To learn about the liquid and solid phases of proteins, and how they might figure in neurodegeneration, tune in to the Alzforum webinar on October 30 at 11 a.m. U.S. Eastern time.

Post navigation

Filter articles published since 2015 by topic, disease, or article type.

Guidlines for filtering

Results are filtered to show all matching articles from a particular category, and to show only articles that match all selected categories.

For instance, if "Biomarkers" and "Genetics" are selected in the Topic category, and "Multiple sclerosis" is selected in the Disease category, all results that match EITHER the Biomarkers OR Genetics Topic category will be shown, but only if they also match the Multiple sclerosis Disease category; i.e. Boolean search of [("Biomarkers" OR "Genetics") AND "multiple sclerosis"]